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LDL-Immune Complexes in Type 2 Diabetes and Vascular Disease

The oxidative modification of LDL has been shown to affect its clearance and exert cytotoxic and immunogenic effect. The objective of our study was to analyse markers of LDL oxidation i.e. soluble LDL containing immune (LDL-IC) complexes in type 2 diabetes with micro- and macrovascular disease. We recruited 69 diabetic patients with coronary artery disease (DM+CAD), 78 nondiabetics with CAD, 47 controls, 27 diabetics with nephropathy and 36 free of complications. OxLDL antibodies and advanced glycated endproducts were measured by ELISA and LDL-IC apo B content after PEG precipitation. We measured a broad range of oxLDL antibody activity in all study groups, but without significant differences. In contrast, the content of apo B, a component of the antigen moiety of oxLDL-IC was higher in CAD and diabetes (+CAD) than that in LDL-IC isolated from controls (p<0.001). LDL-IC did not differ between patients with CAD+DM and CAD patients free of diabetes. LDL-IC level in diabetic patients with or without microangiopathy was significantly higher than that in healthy volunteers (PEG-apo B: 0.278 0.107 vs. 0.165 105 g/l, p<0.002 ; PEG-IgG. 151.7 76 vs. 115.4 62 g/l, p<0.05). However, we did not find a significant difference in the quantity of circulating LDL-IC between the subgroup of diabetic patients with nephropathy/retinopathy and the patients free of microvascular disease (Ab- oxLDL 27.7 10.4 vs. 27.1 9.3 AU, NS ; PEG-apoB 0.324 0.111 vs. 0.287 0.124 g/L, NS ; PEG-IgG 1.68 0.68 vs. 1.42 0.80 g/L, NS). The correlation between AGE content and LDL-IC was positive and statistically significant (r=0.35, p<0.009). We observed a significant but inverse correlation between triglyceride concentration and the amount of LDL-IC in diabetes with CAD (r=-0.32, p<0.016) and in CAD patients (r=-0.35, p<0.002). In patients with early nephropathy a very significant negative correlation between triglycerides and circulating LDL-IC (r=-0.54, p<0.039) was found, but not so in patients with physiological proteinuria. It is known that at high triglyceride level in type 2 diabetes, the majority of LDL is small and dense, thus being more susceptible to oxidative modification. This could be a possible mechanism explaining why more LDL-IC, with a level inversely correlating with triglyceride concentration, are generated in diabetes. Increased level of circulating LDL-IC represent a general risk factor for the general population, including diabetes. LDL-IC measurements in type 2 diabetics plus CAD, with or without microangiopathy showed that diabetic patients are a high-risk population.

diabetes ; oxidized-LDL ; immune complexes

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